全文获取类型
收费全文 | 962篇 |
免费 | 117篇 |
学科分类
生物科学 | 1079篇 |
出版年
2021年 | 8篇 |
2020年 | 10篇 |
2019年 | 8篇 |
2018年 | 9篇 |
2017年 | 8篇 |
2016年 | 13篇 |
2015年 | 23篇 |
2014年 | 16篇 |
2013年 | 34篇 |
2012年 | 43篇 |
2011年 | 52篇 |
2010年 | 26篇 |
2009年 | 38篇 |
2008年 | 39篇 |
2007年 | 37篇 |
2006年 | 48篇 |
2005年 | 26篇 |
2004年 | 30篇 |
2003年 | 29篇 |
2002年 | 41篇 |
2001年 | 25篇 |
2000年 | 32篇 |
1999年 | 24篇 |
1998年 | 11篇 |
1997年 | 9篇 |
1996年 | 12篇 |
1995年 | 12篇 |
1993年 | 9篇 |
1992年 | 17篇 |
1991年 | 21篇 |
1990年 | 22篇 |
1989年 | 15篇 |
1988年 | 18篇 |
1987年 | 13篇 |
1986年 | 17篇 |
1985年 | 17篇 |
1984年 | 16篇 |
1982年 | 14篇 |
1981年 | 17篇 |
1980年 | 14篇 |
1979年 | 15篇 |
1978年 | 8篇 |
1977年 | 12篇 |
1976年 | 16篇 |
1975年 | 9篇 |
1974年 | 18篇 |
1971年 | 13篇 |
1970年 | 11篇 |
1969年 | 11篇 |
1968年 | 7篇 |
排序方式: 共有1079条查询结果,搜索用时 15 毫秒
101.
102.
Pacific halibut collected in the Aleutian Islands, Bering Sea and Gulf of Alaska were used to test the hypothesis of genetic
panmixia for this species in Alaskan marine waters. Nine microsatellite loci and sequence data from the mitochondrial (mtDNA)
control region were analyzed. Eighteen unique mtDNA haplotypes were found with no evidence of geographic population structure.
Using nine microsatellite loci, significant heterogeneity was detected between Aleutian Island Pacific halibut and fish from
the other two regions (F
ST range = 0.007–0.008). Significant F
ST values represent the first genetic evidence of divergent groups of halibut in the central and western Aleutian Archipelago.
No significant genetic differences were found between Pacific halibut in the Gulf of Alaska and the Bering Sea leading to
questions about factors contributing to separation of Aleutian halibut. Previous studies have reported Aleutian oceanographic
conditions at deep inter-island passes leading to ecological discontinuity and unique community structure east and west of
Aleutian passes. Aleutian Pacific halibut genetic structure may result from oceanographic transport mechanisms acting as partial
barriers to gene flow with fish from other Alaskan waters. 相似文献
103.
Jochen Schulze Sebastian Seitz Hiroaki Saito Michael Schneebauer Robert P. Marshall Anke Baranowsky Bjoern Busse Arndt F. Schilling Felix W. Friedrich Joachim Albers Alexander S. Spiro Jozef Zustin Thomas Streichert Kristina Ellwanger Christof Niehrs Michael Amling Roland Baron Thorsten Schinke 《PloS one》2010,5(4)
Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators of this pathway is Dkk1, which antagonizes Wnt signalling through the formation of a ternary complex with the transmembrane receptors Krm1/2 and Lrp5/6, thereby blocking the induction of Wnt signalling by the latter ones. Here we show that Kremen-2 (Krm2) is predominantly expressed in bone, and that its osteoblast-specific over-expression in transgenic mice (Col1a1-Krm2) results in severe osteoporosis. Histomorphometric analysis revealed that osteoblast maturation and bone formation are disturbed in Col1a1-Krm2 mice, whereas bone resorption is increased. In line with these findings, primary osteoblasts derived from Col1a1-Krm2 mice display a cell-autonomous differentiation defect, impaired canonical Wnt signalling and decreased production of the osteoclast inhibitory factor Opg. To determine whether the observed effects of Krm2 on bone remodeling are physiologically relevant, we analyzed the skeletal phenotype of 24 weeks old Krm2-deficient mice and observed high bone mass caused by a more than three-fold increase in bone formation. Taken together, these data identify Krm2 as a regulator of bone remodeling and raise the possibility that antagonizing KRM2 might prove beneficial in patients with bone loss disorders. 相似文献
104.
The specific activity of catalase purified from the peroxisomes of sunflower cotyledons declines in parallel with the total cotyledonary catalase activity during the transition of peroxisomes from glyoxysomal to leaf peroxisomal function. The hematin content of the purified catalase however, remains constant at 4 hematin groups per catalase molecule. The absorbance coefficients of catalase at 404 and 280 nm were determined to be 372 and 540/mM/cm, respectively. 相似文献
105.
Rainer Seitz Friedger von Auer Johannes Blümel Reinhard Burger Anne Buschmann Klaus Dietz Margarethe Heiden Walter E Hitzler Horst Klamm Thomas Kreil Hans Kretzschmar Micha Nübling Ruth Offergeld Georg Pauli Volkmar Schottstedt Peter Volkers Inga Zerr 《Biologicals》2007,35(2):79-97
Variant Creutzfeldt-Jakob disease (vCJD) is an at present inevitably lethal neurodegenerative disease which can only be diagnosed definitely post mortem. The majority of the approximately 200 victims to date have resided in the UK where most contaminated beef materials entered the food chain. Three cases in the UK demonstrated that vCJD can be transmitted by blood transfusion. Since BSE and vCJD have spread to several countries outside the UK, it appears advisable that specific risk assessments be carried out in different countries and geographic areas. This review explains the approach adopted by Germany in assessing the risk and considering precautionary measures. A fundamental premise is that the feeding chain of cattle and the food chain have been successfully and permanently cleared from contaminated material. This raises the question of whether transmissions via blood transfusions could have the potential to perpetuate vCJD in mankind. A model calculation based on actual population data showed, however, that this would not be the case. Moreover, an exclusion of transfusion recipients from blood donation would add very little to the safety of blood transfusions, but would have a considerable impact on blood supply. Therefore, an exclusion of transfusion recipients was not recommended in Germany. 相似文献
106.
Lin SP Coan P da Rocha ST Seitz H Cavaille J Teng PW Takada S Ferguson-Smith AC 《Development (Cambridge, England)》2007,134(2):417-426
Genomic imprinting is an epigenetic mechanism controlling parental-origin-specific gene expression. Perturbing the parental origin of the distal portion of mouse chromosome 12 causes alterations in the dosage of imprinted genes resulting in embryonic lethality and developmental abnormalities of both embryo and placenta. A 1 Mb imprinted domain identified on distal chromosome 12 contains three paternally expressed protein-coding genes and multiple non-coding RNA genes, including snoRNAs and microRNAs, expressed from the maternally inherited chromosome. An intergenic, parental-origin-specific differentially methylated region, the IG-DMR, which is unmethylated on the maternally inherited chromosome, is necessary for the repression of the paternally expressed protein-coding genes and for activation of the maternally expressed non-coding RNAs: its absence causes the maternal chromosome to behave like the paternally inherited one. Here, we characterise the developmental consequences of this epigenotype switch and compare these with phenotypes associated with paternal uniparental disomy of mouse chromosome 12. The results show that the embryonic defects described for uniparental disomy embryos can be attributed to this one cluster of imprinted genes on distal chromosome 12 and that these defects alone, and not the mutant placenta, can cause prenatal lethality. In the placenta, the absence of the IG-DMR has no phenotypic consequence. Loss of repression of the protein-coding genes occurs but the non-coding RNAs are not repressed on the maternally inherited chromosome. This indicates that the mechanism of action of the IG-DMR is different in the embryo and the placenta and suggests that the epigenetic control of imprinting differs in these two lineages. 相似文献
107.
Volkhard Seitz Sigrid Schaper Anja Dr?ge Dido Lenze Michael Hummel Steffen Hennig 《Nucleic acids research》2015,43(20):e135
Two-step PCR procedures are an efficient and well established way to generate amplicon libraries for NGS sequencing. However, there is a high risk of cross-contamination by carry-over of amplicons from first to second amplification rounds, potentially leading to severe misinterpretation of results. Here we describe a new method able to prevent and/or to identify carry-over contaminations by introducing the K-box, a series of three synergistically acting short sequence elements. Our K-boxes are composed of (i) K1 sequences for suppression of contaminations, (ii) K2 sequences for detection of possible residual contaminations and (iii) S sequences acting as separators to avoid amplification bias. In order to demonstrate the effectiveness of our method we analyzed two-step PCR NGS libraries derived from a multiplex PCR system for detection of T-cell receptor beta gene rearrangements. We used this system since it is of high clinical relevance and may be affected by very low amounts of contaminations. Spike-in contaminations are effectively blocked by the K-box even at high rates as demonstrated by ultra-deep sequencing of the amplicons. Thus, we recommend implementation of the K-box in two-step PCR-based NGS systems for research and diagnostic applications demanding high sensitivity and accuracy. 相似文献
108.
James E. Tarver Alexandre Cormier Natalia Pinzón Richard S. Taylor Wilfrid Carré Martina Strittmatter Hervé Seitz Susana M. Coelho J. Mark Cock 《Nucleic acids research》2015,43(13):6384-6398
There is currently convincing evidence that microRNAs have evolved independently in at least six different eukaryotic lineages: animals, land plants, chlorophyte green algae, demosponges, slime molds and brown algae. MicroRNAs from different lineages are not homologous but some structural features are strongly conserved across the eukaryotic tree allowing the application of stringent criteria to identify novel microRNA loci. A large set of 63 microRNA families was identified in the brown alga Ectocarpus based on mapping of RNA-seq data and nine microRNAs were confirmed by northern blotting. The Ectocarpus microRNAs are highly diverse at the sequence level with few multi-gene families, and do not tend to occur in clusters but exhibit some highly conserved structural features such as the presence of a uracil at the first residue. No homologues of Ectocarpus microRNAs were found in other stramenopile genomes indicating that they emerged late in stramenopile evolution and are perhaps specific to the brown algae. The large number of microRNA loci in Ectocarpus is consistent with the developmental complexity of many brown algal species and supports a proposed link between the emergence and expansion of microRNA regulatory systems and the evolution of complex multicellularity. 相似文献
109.
Christoph Gerhardt Johanna Maria Lier Stephan Burmühl Andreas Struchtrup Kathleen Deutschmann Maik Vetter Tristan Leu Sandra Reeg Tilman Grune Ulrich Rüther 《The Journal of cell biology》2015,210(1):1027-1045
Mutations in RPGRIP1L result in severe human diseases called ciliopathies. To unravel the molecular function of RPGRIP1L, we analyzed Rpgrip1l−/− mouse embryos, which display a ciliopathy phenotype and die, at the latest, around birth. In these embryos, cilia-mediated signaling was severely disturbed. Defects in Shh signaling suggested that the Rpgrip1l deficiency causes an impairment of protein degradation and protein processing. Indeed, we detected a cilia-dependent decreased proteasomal activity in the absence of Rpgrip1l. We found different proteasomal components localized to cilia and identified Psmd2, a component of the regulatory proteasomal 19S subunit, as an interaction partner for Rpgrip1l. Quantifications of proteasomal substrates demonstrated that Rpgrip1l regulates proteasomal activity specifically at the basal body. Our study suggests that Rpgrip1l controls ciliary signaling by regulating the activity of the ciliary proteasome via Psmd2. 相似文献
110.
P301L tau expression affects glutamate release and clearance in the hippocampal trisynaptic pathway 下载免费PDF全文
Holly C. Hunsberger Carolyn C. Rudy Seth R. Batten Greg A. Gerhardt Miranda N. Reed 《Journal of neurochemistry》2015,132(2):169-182
Individuals at risk of developing Alzheimer's disease (AD) often exhibit hippocampal hyperexcitability. A growing body of evidence suggests that perturbations in the glutamatergic tripartite synapse may underlie this hyperexcitability. Here, we used a tau mouse model of AD (rTg(TauP301L)4510) to examine the effects of tau pathology on hippocampal glutamate regulation. We found a 40% increase in hippocampal vesicular glutamate transporter, which packages glutamate into vesicles, and has previously been shown to influence glutamate release, and a 40% decrease in hippocampal glutamate transporter 1, the major glutamate transporter responsible for removing glutamate from the extracellular space. To determine whether these alterations affected glutamate regulation in vivo, we measured tonic glutamate levels, potassium‐evoked glutamate release, and glutamate uptake/clearance in the dentate gyrus, cornu ammonis 3(CA3), and cornu ammonis 1(CA1) regions of the hippocampus. P301L tau expression resulted in a 4‐ and 7‐fold increase in potassium‐evoked glutamate release in the dentate gyrus and CA3, respectively, and significantly decreased glutamate clearance in all three regions. Both release and clearance correlated with memory performance in the hippocampal‐dependent Barnes maze task. Alterations in mice expressing P301L were observed at a time when tau pathology was subtle and before readily detectable neuron loss. These data suggest novel mechanisms by which tau may mediate hyperexcitability.